Hepatocyte ATF3 protects against atherosclerosis by regulating HDL and bile acid metabolism
文献类型：期刊论文
| 作者 | Xu, Yanyong2; Li, Yuanyuan1,2,7; Jadhav, Kavita2; Pan, Xiaoli2,3; Zhu, Yingdong2; Hu, Shuwei2; Chen, Shaoru2; Chen, Liuying3; Tang, Yong4; Wang, Helen H.5,6 |
| 刊名 | NATURE METABOLISM
 |
| 出版日期 | 2021-01-18 |
| 页码 | 31 |
| DOI | 10.1038/s42255-020-00331-1 |
| 通讯作者 | Zhang, Yanqiao(yzhang@neomed.edu) |
| 英文摘要 | Activating transcription factor (ATF)3 is known to have an anti-inflammatory function, yet the role of hepatic ATF3 in lipoprotein metabolism or atherosclerosis remains unknown. Here we show that overexpression of human ATF3 in hepatocytes reduces the development of atherosclerosis in Western-diet-fed Ldlr(-/-) or Apoe(-/-) mice, whereas hepatocyte-specific ablation of Atf3 has the opposite effect. We further show that hepatic ATF3 expression is inhibited by hydrocortisone. Mechanistically, hepatocyte ATF3 enhances high-density lipoprotein (HDL) uptake, inhibits intestinal fat and cholesterol absorption and promotes macrophage reverse cholesterol transport by inducing scavenger receptor group B type 1 (SR-BI) and repressing cholesterol 12 alpha-hydroxylase (CYP8B1) in the liver through its interaction with p53 and hepatocyte nuclear factor 4 alpha, respectively. Our data demonstrate that hepatocyte ATF3 is a key regulator of HDL and bile acid metabolism and atherosclerosis. Xu et al. show that liver ATF3 expression is inhibited by hydrocortisone, thus promoting the development of atherosclerosis through effects on HDL cholesterol and bile acid metabolism. |
| WOS关键词 | REVERSE CHOLESTEROL TRANSPORT ; HIGH-DENSITY-LIPOPROTEIN ; ACTIVATING TRANSCRIPTION FACTOR-3 ; DUAL-RELEASE HYDROCORTISONE ; CORONARY-ARTERY-DISEASE ; RECEPTOR-DEFICIENT MICE ; SR-BI ; ADRENAL INSUFFICIENCY ; PREVENTS ATHEROSCLEROSIS ; URSODEOXYCHOLIC ACID |
| 资助项目 | National Institutes of Health[R01DK102619] ; National Institutes of Health[R01HL103227] ; National Institutes of Health[R01HL142086] ; National Institutes of Health[R01DK118941] ; National Institutes of Health[R01DK118805] |
| WOS研究方向 | Endocrinology & Metabolism |
| 语种 | 英语 |
| WOS记录号 | WOS:000610413900006 |
| 出版者 | NATURE RESEARCH |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/295975]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Zhang, Yanqiao |
| 作者单位 | 1.Chinese Acad Sci, Inst Drug Discovery & Dev, Zhongshan Inst Drug Discovery, Zhongshan, Peoples R China 2.Northeast Ohio Med Univ, Dept Integrat Med Sci, Rootstown, OH 44272 USA 3.Huazhong Univ Sci & Technol, Union Hosp, Div Gastroenterol, Tongji Med Coll, Wuhan, Peoples R China 4.Huazhong Univ Sci & Technol, Union Hosp, Dept Hepatobiliary Surg, Tongji Med Coll, Wuhan, Peoples R China 5.Marion Bessin Liver Res Ctr, Dept Med & Genet, Bronx, NY USA 6.Albert Einstein Coll Med, Bronx, NY 10467 USA 7.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xu, Yanyong,Li, Yuanyuan,Jadhav, Kavita,et al. Hepatocyte ATF3 protects against atherosclerosis by regulating HDL and bile acid metabolism[J]. NATURE METABOLISM,2021:31. |
| APA | Xu, Yanyong.,Li, Yuanyuan.,Jadhav, Kavita.,Pan, Xiaoli.,Zhu, Yingdong.,...&Zhang, Yanqiao.(2021).Hepatocyte ATF3 protects against atherosclerosis by regulating HDL and bile acid metabolism.NATURE METABOLISM,31. |
| MLA | Xu, Yanyong,et al."Hepatocyte ATF3 protects against atherosclerosis by regulating HDL and bile acid metabolism".NATURE METABOLISM (2021):31. |
入库方式： OAI收割
来源：上海药物研究所
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